The Gene Genies

Could your cellular blueprint hold the secret to eternal youth?

It's funny that genes have been linked to whether or not we'll end up being neurotic (on top of whether we'll have blond hair, Olympic-level musculature, or an increased risk of breast cancer) since, beauty-wise, genes seem to be the latest thing worth getting neurotic about. Turns out the genes of skin cells, being relatively accessible, are also surprisingly mutable. Consider this: Even the tiny dose of UV light you encounter on a sunny morning commute can cause DNA damage, leading to a cascade effect of aging—spots, lines, even skin cancer. (Are you reaching for the sunscreen yet?) Or this: Last year, by manipulating DNA, a Stanford scientist pulled off the lab-rat equivalent of turning Betty White into Scarlett Johansson—he made the skin of old mice young again in a mere two weeks. (More on that later.) Call me neurotic, but I'm vaguely jealous of those babe-ified rodents.

"Until now, we've focused on freeradical scavenging, sunscreen, premature aging—that's what we know," says a visibly excited Daniel Maes, PhD, the senior vice president of research and development at Estée Lauder. "Now we've entered the era of genetic aging." At the moment, beauty companies are diving into genetargeting territory with incredible optimism, not to mention speed—and they're beating big pharma to the checkout line. "Beauty companies are able to get products on the market early because they're not regulated by the FDA," says MIT biologist and leading genetics researcher Leonard Guarente, PhD. "In a way, they're the vanguard."

The Miami Valley Innovation Center— a sprawling Procter & Gamble think tank outside of Cincinnati—aims to lead the charge. Here a team of "gene jockeys" analyzes hundreds of people's genetic fingerprints via a NASA-worthy technology called GeneChips. Jay Tiesman, PhD, a P&G scientist and top "jockey," agrees to demonstrate how this works by "tapestripping" yours truly. This involves pressing circle after circle of adhesive disks to my cheek in order to peel off dead cells and get down to active ones where DNA is functioning. Tiesman distracts me from the angry red bull's-eye that is emerging on my face ( Jay, if you're reading this: It lasted two whole days!) with Genetics 101: Every cell in our bodies contains the same two interlocking strands of DNA— nearly 34,000 genes. But not every gene is active in every cell; the ones that are active determine the cell's identity and function, be it muscle, skin, liver, or even cancer. More than 20,000 are in play in skin, some more than others. Like everything else, genes weaken with age. They can slow down or get stuck in the "on" or "off" position—hence genetic aging.

GeneChips measure skin's levels of RNA, the messenger molecules through which DNA dispatches its orders, telling cells to replicate, pump out collagen, or even die. Analyzing GeneChips is "like looking at 54,000 dimmer switches," Tiesman says. "Are they saying MAKE COLLAGEN or make collagen?"

Tiesman spares me the calculations on my "stripped" cells (suffice it to say that 54,000 rows on a spreadsheet yield some 6.5 million bits of data or, as one P&G researcher put it, "a hairball of information"), but a few weeks later, he calls with the verdict. For the purposes of comparison, he had measured my numbers against those of Chelsea, a lab assistant who, like me, is 32. Ultimately, we tied: While I had a higher expression of genes that control skin's barrier-building fatty acids and cholesterol, Chelsea had less inflammation.

Sylvie Lancrenon

To vastly oversimplify, this means that Chelsea and I are both on track to end up being Golden Girls in our golden years—but we'll have our spots and lines for different reasons. The company's most surprising GeneChip discovery has been not so much what happens when we age (sagging, wrinkles, dehydration—genetics affect all of these little marvels), but which gene- influenced factors seem to be doing the most damage. The two main culprits are inflammation (my problem) and an impaired moisture barrier (Chelsea's). "The barrier is skin's first line of defense. It keeps good stuff in and bad stuff—bacteria, fungus, harsh chemicals, allergens, pollution, cigarette smoke—out," says Rosemarie Osborne, a P&G Beauty principal scientist. "When the barrier is compromised, skin focuses entirely on restoring it, which slows down everything else."

What does P&G propose to do about it? The new Olay Professional Pro-X line was cooked up to compensate for these changes. Hexamidine, one of its star ingredients, jump-starts the enzymes that produce barrier-friendly lipids. (Hexamidine also exemplifies P&G's wacky but brilliant tendency to cross-pollinate: Giving new meaning to the phrase "softer than a baby's bottom," the compound was originally developed to stabilize skin conditioners in Pampers.)

As for the daily oxidative assault on our DNA, chances are your skin-care regimen is already providing some assistance: antioxidants such as vitamin C, green tea, and pomegranate help disarm renegade free radicals. Plus, the body is built with its own repairmen: Pac-Man–style enzymes that literally chomp out damaged segments and flip in new ones. Skin-care lines Nia 24 and Canyon Ranch Your Transformation aim to aid this constant grooming process by supplying niacin, or vitamin B3, a building block of skin's own DNA repair tool kit.

According to MIT's Guarente, however, all these damage do-gooders may be beside the point. "No known substance can cause genes to repair themselves," he says. "There are a lot of things going wrong at the same time in cells. You could repair one thing, but something else could be just as bad."

Instead, some scientists are targeting specific age-regulating genes—which brings us back to those young-again miracle mice. "A lot of people have the idea that aging is the accumulation of wear and tear on the body, and that's certainly true," says Howard Chang, MD, PhD, an associate professor of dermatology at the Stanford University School of Medicine. "But besides accumulated damage, there's also the separate idea that some genes might actually be controlling the overall life span of an organism by coordinating the rate of aging." When Chang's team applied a topical chemical to block NF-kappaB (a signal that turns on with age and controls the activity of hundreds of genes), the mice's skin looked and behaved like that of newborns: thicker, with more cell division and the same active genes seen in young mice.

Sylvie Lancrenon

Before you book your flight to Palo Alto, bear in mind that Chang's mice were genetically engineered to respond to the chemical. (It wouldn't work on normal mice, let alone humans.) And the consequences of blocking this process are still unclear. Nonetheless, the takeaway is breathtaking: "Aging is surprisingly plastic," Chang says. "Tissue can revert back to its youthful state."

NF-kappaB may be a long way from becoming a household word, but another genetic age-determiner is not: sirtuins. This family of seven "longevity genes" (plus the proteins they encode for) regulates DNA repair, recombination, and aging, and could be the key to aging-related diseases, such as type 2 diabetes, obesity, and Alzheimer's.

In 2000, Guarente led a landmark study in which a Spartan diet of 1,000 to 1,500 daily calories—believed for decades to extend life span—was shown to work, at least in part, by activating sirtuins. Starvation sets off an alarm in the cell, forcing it to work economically and slowing down cellular division. In 2003, Harvard Medical School associate professor of pathology David Sinclair, PhD (a former Guarente mentee), discovered the sirtuin-activating powers of resveratrol, the polyphenol found in red wine. Resveratrol extends the life span of mice by 24 percent and that of other animals, including flies and worms, by as much as 59 percent. At press time, a phase two clinical trial of an oral resveratrol supplement for humans was nearing completion; as of now, though, we'd have to quaff roughly 1,500 bottles of vino per day—too much, even for me—to get comparable results.

So far, skin-care companies are focused on SIRT1, the sirtuin that, like a cautious governess, reins in excessive cellular proliferation to allow cells to complete their repair cycle. Dior, Avon, and London's Ren Clean Bio Active Skincare all offer various sirtuin-stimulating products, but Estée Lauder has made these still-mysterious proteins its primary antiaging target. "We've found a gold mine, and we're exploring it to the end," Maes says.

Sirtuins, in fact, are the perfect skin solution for Maes, who seems to support the "tortoise and the hare" model of cellular rejuvenation. In a world of retinoids, acid peels, and microdermabrasion—all intended to speed cell turnover in order to reveal a spanking-new, unblemished surface—he wants to do the opposite: slow it down, giving cells extra time to repair their own DNA damage before replication. Yes, you read right—this would mean that high-strength retinoids, every dermatologist's best friend, may be causing aging in the long run. "We know that cells are programmed to reproduce a very specific number of times," Maes says. "Speeding them up uses up your potential for cellular division so that, when you get older, your skin will be worn out."

Sylvie Lancrenon

Last year, Lauder introduced Re-Nutriv Ultimate Youth Creme, a $250 wondersalve packed with a proprietary version of resveratrol. The brand's new Time Zone (at $58, significantly more wallet-friendly) does the trick with a patented rice extract; in vitro tests showed a 200 percent increase in collagen synthesis and 79 percent fewer cell deaths after UV exposure.

Meanwhile, back in the lab, even resveratrol is aging out. The new kid on the block has a wonky name (SRT1720) but major muscle. In a study published in November, mice who ate a high-fat, high-calorie meal plan for 15 weeks—plus regular doses of SRT1720—emerged with the traits of younger, healthier rodents: lower cholesterol, less obesity-related disease, and better insulin sensitivity. If it can do that on the inside, imagine what it could do for your face.

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